Phenotype, genotype, treatment, and survival outcomes in patients with X-linked inhibitor of apoptosis deficiency.
HLH
HSCT
IBD
X-linked inhibitor of apoptosis
XIAP deficiency
adult
conservative treatment
phenotype
primary immunodeficiency
survival outcomes
therapy
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
06
07
2021
revised:
06
10
2021
accepted:
13
10
2021
pubmed:
18
12
2021
medline:
10
8
2022
entrez:
17
12
2021
Statut:
ppublish
Résumé
X-linked inhibitor of apoptosis (XIAP) deficiency is a rare primary immunodeficiency disease caused by XIAP gene mutations. A broad range of phenotype, severity, and age at onset present challenges for patient management. We sought to characterize the phenotype, treatment, and survival outcomes of XIAP deficiency and to assess parameters influencing prognosis. Data published from 2006 to 2020 were retrospectively analyzed. A total of 167 patients from 117 families with XIAP deficiency were reported with 90 different mutations. A wide spectrum of clinical features were seen, of which hemophagocytic lymphohistiocytosis (HLH) and inflammatory bowel disease were the most common. Patients frequently developed multiple features with no clear genotype-phenotype correlation. A total of 117 patients were managed conservatively and 50 underwent hematopoietic stem-cell transplantation (HSCT), with respective overall survival probabilities of 90% and 53% at age 16 years. The predominant indication for HSCT was early-onset HLH. Active HLH and myeloablative conditioning regimens increased HSCT-related mortality, although HSCT outcome was much better after 2015 than before. For conservatively managed patients reaching adulthood, survival probabilities were 86% at age 30 years and 37% by age 52 years, with worse outcomes for patients developing the disease before the age of 5 years or with new disease features in adulthood. Nine asymptomatic mutation carriers with a median age of 13.5 years were identified. Our study demonstrates the variable nature of XIAP deficiency, which evolves over life for individual patients. Better therapeutic strategies and prospective studies are required to reduce morbidity and mortality and improve decision making and long-term outcomes for patients with XIAP deficiency.
Sections du résumé
BACKGROUND
X-linked inhibitor of apoptosis (XIAP) deficiency is a rare primary immunodeficiency disease caused by XIAP gene mutations. A broad range of phenotype, severity, and age at onset present challenges for patient management.
OBJECTIVE
We sought to characterize the phenotype, treatment, and survival outcomes of XIAP deficiency and to assess parameters influencing prognosis.
METHODS
Data published from 2006 to 2020 were retrospectively analyzed.
RESULTS
A total of 167 patients from 117 families with XIAP deficiency were reported with 90 different mutations. A wide spectrum of clinical features were seen, of which hemophagocytic lymphohistiocytosis (HLH) and inflammatory bowel disease were the most common. Patients frequently developed multiple features with no clear genotype-phenotype correlation. A total of 117 patients were managed conservatively and 50 underwent hematopoietic stem-cell transplantation (HSCT), with respective overall survival probabilities of 90% and 53% at age 16 years. The predominant indication for HSCT was early-onset HLH. Active HLH and myeloablative conditioning regimens increased HSCT-related mortality, although HSCT outcome was much better after 2015 than before. For conservatively managed patients reaching adulthood, survival probabilities were 86% at age 30 years and 37% by age 52 years, with worse outcomes for patients developing the disease before the age of 5 years or with new disease features in adulthood. Nine asymptomatic mutation carriers with a median age of 13.5 years were identified.
CONCLUSIONS
Our study demonstrates the variable nature of XIAP deficiency, which evolves over life for individual patients. Better therapeutic strategies and prospective studies are required to reduce morbidity and mortality and improve decision making and long-term outcomes for patients with XIAP deficiency.
Identifiants
pubmed: 34920033
pii: S0091-6749(21)02597-5
doi: 10.1016/j.jaci.2021.10.037
pii:
doi:
Substances chimiques
X-Linked Inhibitor of Apoptosis Protein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
456-466Investigateurs
Anna Sediva
(A)
Benedicte Neven
(B)
Fabian Hauck
(F)
Klaus Warnatz
(K)
Malgorzata Pac
(M)
Maria Carrabba
(M)
Pere Palacin
(P)
Peter Jandus
(P)
Ann Gardulf
(A)
Nizar Mahlaoui
(N)
Martine Pergent
(M)
Catharina Schutz
(C)
Svetlana Sharapova
(S)
Lougaris Vassilios
(L)
Fabio Candotti
(F)
Stephano Volpi
(S)
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022. Published by Elsevier Inc.